Sitagliptin is chemically referred to as 7-[1-oxo-3R-3-amino-4-(2,4,5-trifluorophenyl)butyl]-3-trifluoromethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine, and is shown in formula 1. Sitagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor for treatment of type-II diabetes mellitus clinically developed by Merck & Co Inc.

In the process of preparing sitagliptin, construction of chiral amino is a key point of synthetic route. The method of constructing chiral amino in the process of preparing sitagliptin is as follows:
Route I: (Reference: WO2004/085378)
In the route according to WO2004/085378, constructing chiral amino of sitagliptin is implemented by a hydrogenation reduction reaction with metal rhodium and chiral ferrocenyl diphosphine. But disadvantages of the method are increased costs and difficulty in being suitable for industrial production due to use of two expensive reagents including metal rhodium and chiral ferrocene ligand.

Route II: (Reference: WO2004/085661)

In the route according to WO2004/085661, S-benzene ammonia amide as a chiral auxiliary is introduced and conducted a catalytic hydrogenation by platinum oxide to induce the desired chiral amino, to produce sitagliptin by debenzylation. But disadvantages of the method are increased costs and difficulty in being suitable for industrial production due to use of the precious metal platinum oxide as the catalyst.
Route III: (Reference: WO2009/085990)

In the route according to WO2009/085990, a chiral auxiliary is R-α-methylbenzylamine instead of S-benzene ammonia amide. But the chiral amino is similarly induced by expensive platinum oxide as catalyst.
It has been reported from the prior art to use several methods for preparing sitagliptin. But they have one or more disadvantages, such as use of expensive reagents (platinum oxide, rhodium catalyst etc.), and/or addition of more protection steps. So it is necessary to develop simple and more economical synthetic routes to be suitable for industrial production.